Schizophrenia (split personality) is a kind of endogenous psychosis, and it is developed mainly during adolescence, and after a chronic course, the personality of patient is progressively decayed, and some of patients may culminate in a mental decay. The symptoms of this disease are, for example, positive symptoms often observed during the early stage of the disease such as hallucination, delusion, etc., or negative symptoms such as apathy and withdrawal, or cognitive dysfunction such as impairments of concentration and learning abilities, etc. Moreover, there are other symptoms such as depression, anxiety, etc. as related symptoms thereof.
Medication is mainly employed in the treatment of schizophrenia, but the treatment of schizophrenia should be continued for a long time, and even though schizophrenia is once healed, there is a large risk of reoccurring of schizophrenia after drug withdrawal so that it is necessary to continue the medication forever. Therefore, any side effects of medication may always be serious problems, and based on this perspective, it has been desired to develop a medicine being suitable for prolonged medication.
The agents for treatment of schizophrenia are various medicaments such as ones classified in the category of antipsychotic, for example, phenothiazine derivatives (e.g., chlorpromazine, methoxy-promazine, etc.), thioxanthin derivatives having a similar structure to phenothiazine (e.g., chlorprothixene, flupentixol, etc.), benzamide derivatives (e.g., sulpiride, sultopride, etc.), thienodiazepine derivatives (e.g., clotiazepam, etizolam, etc.), and further butyrophenone derivatives (e.g., haloperidol, triperidol, etc.), diphenylbutylamine derivatives (e.g., pimozide, etc.), etc.
However, phenothiazine derivatives, phenothiazine analogues, and butyrophenone derivatives may cause serious side effects of extrapyramidal symptoms showing parkinsonism such as the stiff gait of skeletal muscles, tremor of muscles, lack of facial expression, salivation, etc. Further, diphenylbutylamine derivatives may cause extrapyramidal symptoms in addition to insomnia. In addition, these conventional antipsychotics may be effective on only some of symptoms among positive symptoms, negative symptoms, cognitive dysfunctions of schizophrenia, and there has been no drug being effective on all of these symptoms.
Therefore, it has been desired to develop a safe medicament which exhibits an excellent effect on various schizophrenia as an antipsychotic without causing side effects such as extrapyramidal symptoms.
On the other hand, it has been known that the imide derivative of the following formula, which was found by the co-workers of the present inventors, may be useful as an antipsychotic (c.f., neuroleptic agent, antiaxiety, etc.), especially as an agent for treatment of schizophrenia, senile insanity, manic depressive psychoses, and nervous breakdown (U.S. Pat. No. 5,532,372).
wherein Z is
D is a group of the formula: —(CH2)p-A-(CH2)q—,
etc., andAr is an aromatic group, or an aromatic heterocyclic group, etc.